Pterostilbene, a natural analogue of resveratrol, potently inhibits 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin carcinogenesis.

Abstract

We reported previously that pterostilbene, a natural analogue of resveratrol from blueberries, strongly suppressed lipopolysaccharide-induced up-expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine macrophages. In this study, we further investigated pterostilbene's molecular mechanism of action and its anti-tumor properties. Pretreatment with pterostilbene has resulted in the reduction of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced nuclear translocation of the nuclear factor-κB (NFκB) subunits. Pterostilbene also reduced TPA-induced phosphorylation of IκBα and p65 and caused subsequent degradation of IκBα. Moreover, pterostilbene markedly suppressed TPA-induced activation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK)1/2, phosphatidylinositol 3-kinase (PI3K) and Akt, which are upstream of NFκB and activator protein 1 (AP-1). Furthermore, pterostilbene significantly inhibited 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 weeks. The presented data has, for the first time, revealed that pterostilbene is an effective anti-tumor agent that functions by downregulating inflammatory iNOS and COX-2 gene expression in mouse skin. It is suggested that pterostilbene is a novel functional agent capable of preventing inflammation-associated tumorigenesis.

• Authors: Mei-Ling Tsai, Ching-Shu Lai, Yen-Hui Chang, Wei-Jen Chen, Chi-Tang Ho, Min-Hsiung Pan
• Journal: Food & function (Food Funct) Vol. 3 Issue 11 Pg. 1185-94 (Nov 2012) ISSN: 2042-650X [Electronic] England
• PMID: 22842666 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• NF-kappa B
• Protein Kinase Inhibitors
• Stilbenes
• pterostilbene
• 9,10-Dimethyl-1,2-benzanthracene
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Tetradecanoylphorbol Acetate
• Resveratrol

Topics

• 9,10-Dimethyl-1,2-benzanthracene
• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Cell Proliferation (drug effects)
• Cyclooxygenase 2 (genetics)
• Down-Regulation (drug effects)
• Female
• Inflammation
• Mice
• Mice, Inbred ICR
• NF-kappa B (antagonists & inhibitors)
• Nitric Oxide Synthase Type II (genetics)
• Protein Kinase Inhibitors (pharmacology)
• Resveratrol
• Skin (enzymology, pathology)
• Skin Neoplasms (chemically induced, pathology, prevention & control)
• Stilbenes (pharmacology)
• Tetradecanoylphorbol Acetate